Many useful opthalmic compounds are solids. Those solids which are soluble in ophthalmic carriers or vehicles present little or no difficulty when preparing a formulation for ophthalmic use. However, those solids which are insoluble in opthalmic carriers must be formulated as suspensions in order to obtain a proper delivery system. Moreover, forms of useful opthalmic compounds which are insoluble in ophthalmic carriers are often found desirable in order to prolong the particular therapeutic action of the compound. Consequently, providing acceptable suspensions of useful ophthalmic compounds is a goal of pharmaceutical formulation.
An acceptable ophthalmic suspension possesses certain essential characteristics, among which are: that the suspended material should not settle too rapidly from the carrier to be available in the required concentration in the carrier for effective administration to the eye of the patient; that the particles of suspended material which do finally settle to the bottom of the vessel holding the suspension must not form an intractable hard cake but should be readily redispersed into a uniform suspension when the vessel is shaken; and that the total suspension must not be too viscous for efficient administration to the eye of the patient, but should pour freely.
Suspensions are prepared by use of either, vehicles structured to maintain discrete particles more or less permanently in suspension, without agglomeration or flocculation, or by the application of known principles of formulation chemistry of produce vehicles which permit flocs to form and settle, but in which they are easily resuspended with slight agitation and remain uniformly dispersed or suspended during the period required for therapeutic administration. In this latter approach, flocculating agents are used in preparing the vehicle or carrier. However, depending upon the type of medicinal product employed, particular ratios of medicament, carrier and flocculating agent must be employed. These critical ratios cannot be determined beforehand and with some medicaments are extremely difficult to obtain at all.
There is a known anti-inflammatory agent useful in therapeutic treatment of inflammatory diseases of the eye; namely 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolyl acetic acid, which is insoluble in conventional ophthalmic carriers and consequently must be employed in the form of suspensions. However, use of this medicament has been impeded by the fact that it does not readily form acceptable suspensions in vehicles containing flocculating agents in the proportions normally employed in ophthalmic suspensions.